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Published on: June 14, 2016
Signal transduction pathways mediating mucin secretion from intestinal goblet cells
1Division of Biological Sciences, University of Missouri, Columbia 65211.
Insights
Cholinergic stimulation enhances mucin secretion in HT29-18N2 goblet cells via a non-compound exocytotic pathway, independent of protein kinase C. This reveals distinct signaling mechanisms for goblet cell responses.
Area of Science:
- Cell Biology
- Gastroenterology
- Signal Transduction
Background:
- Goblet cells are crucial for intestinal mucus secretion.
- Understanding goblet cell secretion pathways is vital for gut health research.
Purpose of the Study:
- To investigate the signaling pathways regulating mucin secretion in HT29-18N2 goblet cells.
- To differentiate between compound and non-compound exocytotic pathways in goblet cell secretion.
Main Methods:
- Utilized mucin-specific immunoassays.
- Employed whole-mount immunocytochemistry.
- Performed morphometric quantification of intracellular mucous granule stores.
- Assessed the role of protein kinase C (PKC) and calcium ionophore A23187.
Main Results:
- Cholinergic stimulation significantly increased mucin secretion.
- Secretory response was mediated by a non-compound exocytotic pathway, not involving PKC.
- Calcium ionophore A23187 also induced secretion via a non-compound exocytotic route.
- Phorbol 12-myristate 13-acetate (PKC activator) stimulated secretion through a compound exocytotic pathway.
Conclusions:
- Cholinergic stimulation triggers mucin secretion in goblet cells through a distinct non-compound exocytotic pathway.
- Goblet cell secretion involves multiple signaling cascades, including PKC-dependent and independent routes.
- These findings offer insights into the complex regulation of intestinal mucus production.
Abstract:
Cholinergic stimulation of the HT29-18N2 goblet cell line increased mucin secretion as assessed: (1) with a mucin-specific immunoassay, (2) using whole-mount immunocytochemistry, or (3) by morphometric quantification of intracellular mucous granule stores. Cholinergic stimulation did not, however, result in the apical plasmalemmal membrane cavitation that is characteristic of recent compound exocytotic activity. The response was not dependent on protein kinase C activation since it was not inhibited by the kinase C antagonist H7 or potentiated by the diacylglycerol kinase antagonist R59022. Calcium ionophore A23187 also accelerated mucin secretion by a noncompound exocytotic pathway. Activation of protein kinase C by phorbol 12-myristate 13-acetate, on the other hand, increased mucin secretion by a compound exocytotic pathway. The results provide insight into the signal transduction pathways underlying secretory responses of goblet cells observed in situ.
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